Elsevier

Journal of Hepatology

Volume 57, Issue 6, December 2012, Pages 1244-1250
Journal of Hepatology

Research Article
Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma

https://doi.org/10.1016/j.jhep.2012.07.017Get rights and content

Background & Aims

Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma. In order to maximize its therapeutic efficacy, doxorubicin-loaded drug-eluting beads have been developed to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. The purpose of this study was to evaluate the efficacy and safety of drug-eluting bead (DC bead®) TACE in comparison with conventional TACE (cTACE).

Methods

A total of 129 patients who underwent TACE between August 2008 and February 2011 were enrolled. We compared HCC patients who underwent TACE with DC bead® (n = 60) to controls who received cTACE (n = 69). The primary end points were treatment response and treatment-related adverse events. The secondary end point was time to progression.

Results

The treatment response in the DC bead® group was significantly higher than that of the cTACE group (p <0.001). The time to progression was significantly better in the DC bead® group than in the cTACE group (11.7 and 7.6 months, respectively, p = 0.018). Subgroup analysis showed that in intermediate-stage HCC, DC bead® treatment resulted in a significantly better treatment response and longer time to progression than cTACE (p <0.001 and 0.038, respectively). However, there was no statistically significant difference in liver toxicity between the DC bead® and cTACE group (p >0.05).

Conclusions

TACE with DC bead® showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in hepatic treatment-related toxicities. DC bead® TACE thus appears to be a feasible and promising approach to the treatment of HCC.

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common cancer with an increasing incidence worldwide, and is the third leading cause of cancer-related death [1], [2]. Despite the widespread use of surveillance programs in at-risk populations, more than half of the patients with HCC are diagnosed late and curative therapies such as resection, transplantation, or radiofrequency ablation (RFA) can be applied in fewer than 30% of the cases [3].

Transarterial chemoembolization (TACE) is widely used to treat HCC patients who are not suitable candidates for curative treatments [4], [5]. The rationale for TACE is that the intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, will result in a strong cytotoxic effect combined with ischemia (“conventional TACE”) [6], [7]. A meta-analysis of randomized controlled trials (RCTs) comparing TACE with the best supportive care showed a distinct survival benefit for TACE in properly selected patients [8].

Recently, drug-eluting beads (DC bead®, Biocompatibles, Surrey, UK) for the transcatheter treatment of HCC have been developed to deliver higher doses of chemotherapeutic agent and to prolong contact time with the tumor. DC bead® has the ability to actively sequester doxorubicin hydrochloride from solution and release it in a controlled and sustained fashion [9]. Treatment with DC bead® loaded with doxorubicin (DEBDOX) has been shown to substantially diminish the amount of chemotherapeutic agent that reaches the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events [10], [11]. Western experiences have also suggested that DC bead® offers superior anticancer activity as compared to bland embolization or conventional TACE (cTACE) [12].

To date, limited data are available concerning the use of TACE with DC bead® in Asia. We previously reported preliminary results regarding the short-term tumor response and liver toxicity of DC bead®-based TACE. Patients in Korea treated with DC bead® for large (>5 cm) or multinodular HCC showed significantly higher objective response rates compared with those treated with cTACE [13]. In the present study, we evaluated the efficacy, safety, and overall survival benefit of DEBDOX treatment in comparison with cTACE in HCC patients in stages A or B of the Barcelona Clinic for Liver Cancer (BCLC) staging system.

Section snippets

Study design

This retrospective cohort analysis was conducted on 129 HCC patients who were treated with TACE-based therapy from August 2008 to February 2011 at the Catholic University Medical Center of Korea. The median duration of follow-up was 18 months (range, 5.0–37.2 months). The eligibility criteria were as follows; (1) confirmed diagnosis and stage of HCC according to non-invasive diagnostic criteria of the American Association for the Study of Liver Disease (AASLD) guidelines and the BCLC staging

Clinical characteristics of the HCC patients

The study included 90 males and 39 females. The mean age was 60 ± 10 years. The clinical characteristics of the 129 patients who underwent TACE are shown in Table 1. The mean age was 59.2 ± 10.3 years in the DEBDOX group and 61.4 ± 10.8 years in the cTACE group. Male gender and hepatitis B virus infection predominated in both groups. More than 92% of the patients had Child–Pugh class A liver function. The mean tumor diameter was 4.6 ± 3.0 cm. The BCLC stage of the patients consisted of stages A (42.6%) and

Discussion

TACE has been widely used as a standard treatment for HCC patients who are not suitable candidates for curative treatments and also as a bridge to liver transplantation. The rationale for TACE is that the strong cytotoxic effect combined with ischemia, followed by chemoembolization of the hepatic artery, will result in therapeutic efficacy and survival benefit compared with supportive care [17].

The recent introduction of DC bead® has provided a valuable alternative to prolong the overall

Ethics approval

Ethics approval was provided by the institutional Ethics Review Board, The Catholic University of Korea (KC11RIST0452).

Financial support

This work was supported by a National R & D Program grant for cancer control, Ministry of Health, Welfare and Family Affairs, Republic of Korea (R0620390-1).

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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